Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitor.
We report the identification of KD5170, a potent mercaptoketone-based Class I and II-histone deacetylase inhibitor that demonstrates broad spectrum cytotoxic activity against a range of human tumor-derived cell lines. KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v. dose and inhibition of tumor growth following chronic dosing.
Payne
Joseph E
JE
Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
Bonnefous
Céline
C
Hassig
Christian A
CA
Symons
Kent T
KT
Guo
Xin
X
Nguyen
Phan-Manh
PM
Annable
Tami
T
Wash
Paul L
PL
Hoffman
Timothy Z
TZ
Rao
Tadimeti S
TS
Shiau
Andrew K
AK
Malecha
James W
JW
Noble
Stewart A
SA
Hager
Jeffrey H
JH
Smith
Nicholas D
ND
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C530801:KD 5170; D011355:Prodrugs; D011725:Pyridines; D013449:Sulfonamides